Researchers at Mayo Clinic have developed a promising gene-editing therapy capable of directly correcting a genetic mutation responsible for autosomal dominant polycystic kidney disease (ADPKD), the most common inherited kidney disorder. A single administration of the gene therapy slowed the growth of kidney cysts, improved heart and liver health, and extended survival in preclinical models of ADPKD. Notably, the researchers found no evidence of harmful genetic changes outside the target or significant immune reactions. "Our results suggest that, in the future, this approach could become a treatment capable of substantially altering the course of the disease," states Dr. Li. Many patients also develop complications outside the kidneys, such as an enlarged heart and liver disease. Current treatments can slow the progression of the disease but do not address its genetic cause. The disease is mainly caused by mutations in the PKD1 or PKD2 genes and leads to the progressive growth of fluid-filled cysts in the kidneys, often resulting in kidney failure. This scientific advance against autosomal dominant polycystic kidney disease was achieved through CRISPR technology. Mayo Clinic researchers applied base editing to correct the PKD1 gene mutation, leading to a reduction in cysts and improved survival in biological models. The new gene-editing strategy from Mayo Clinic addresses the root cause of the disease, overcoming the limitations of current palliative treatments. "It allows us to maximize the benefit and minimize the risk," the study notes. This work advances Mayo Clinic's Genesis initiative, which aims to prevent organ failure and restore function through regenerative medicine, precision genomics, and advanced therapies. Ongoing studies are focused on refining base-editing tools to address a wider range of PKD-associated mutations, assessing whether the treatment can be effective after cysts have already formed, and developing alternative delivery methods, including non-viral options like nanoparticles, to support its future clinical use. "If these approaches are successfully translated to humans, they could reduce or even eliminate the need for chronic medication, delay kidney failure, and significantly improve the quality of life for patients with ADPKD," concludes Dr. Li.
